JCT  Vol.6 No.5 , May 2015
FAS-670 Gene Promoter Region Polymorphism in Cervical Intraepithelial Neoplasia Grade 3 (CIN 3) and Invasive Cervical Cancer
ABSTRACT

The human papillomavirus (HPV) is the etiologic agent of genital cancer, but alone it is incapable of inducing oncogenesis. Rather, progression to invasive lesions is associated with host immunity and interference in the process of cellular apoptosis. Among the several genes involved in cell death, theFAS gene appears to be an important factor. The aim of this study was to evaluate whether there is an association between polymorphisms of the FAS-670 gene promoter region and preinvasive and invasive lesions of the cervix. The FAS gene was evaluated for the presence of polymorphisms using polymerase chain reaction and restriction fragment length polymorphism techniques in 225 blood samples for the control group, as well as cervical tissue from patients with cervical intraepithelial neoplasia grade 3 (CIN 3; 75 cases) or invasive carcinoma (214 cases). The AG genotype of the FAS-670 gene promoter region was significantly more frequent in women with CIN 3, with an estimated risk of three times (OR = 3.0). No difference, however, was observed in the control group and women with cervical cancer. In women with cancer, the genotypes were similar in the different histological types and degree of tumor differentiation. Assessing allelic distribution (A or G), we observed no difference in frequency of genotypes in studied groups. These data suggest that polymorphism of the promoter region of the FAS-670 gene is associated with increased risk of CIN 3, but not for invasive cancer of the cervix.


Cite this paper
Fedrizzi, E. , Zucchi, F. , Brenna, S. , Carvalho, C. , Silva, F. , Costa, A. and Silva, I. (2015) FAS-670 Gene Promoter Region Polymorphism in Cervical Intraepithelial Neoplasia Grade 3 (CIN 3) and Invasive Cervical Cancer. Journal of Cancer Therapy, 6, 434-445. doi: 10.4236/jct.2015.65047.
References
[1]   Franco, E.L. (1995) Epidemiology of Breast and Gynecological Cancer. In: Abrao, F.S., Ed., Treaty of Genital and Breast Cancer, Editora Roca, Sao Paulo, 145-167.

[2]   Bruni, L., Barrionuevo-Rosas, L., Serrano, B., et al. (2014) ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in Brazil, Summary Report 2014.

[3]   Zur Hausen, H. (1986) Intracellular Survilance of Persisting Viral Infection: Human Genital Cancer Resulting from a Failing Cellular Control of Papillomavirus Gene Expression. Lancet, ii, 489-491.
http://dx.doi.org/10.1016/S0140-6736(86)90360-0

[4]   Herrington, C.S. (1994) Human Papillomaviruses and Cervical Neoplasia. I: Classification, Virology, Pathology and Epidemiology. Journal of Clinical Pathology, 47, 1066-1072.
http://dx.doi.org/10.1136/jcp.47.12.1066

[5]   Walboomers, J.M.M., Jacobs, M.V., Manos, M.M., et al. (1999) Human Papillomavirus Is a Necessary Cause of Invasive Cervical Cancer Worldwide. The Journal of Pathology, 189, 12-19.
http://dx.doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F

[6]   Mougin, C., Dalstein, V., Pretet, J.L., et al. (2001) Epidemiology of Cervical Papillomavirus Infections. Recent Knowledge. La Presse Médicale, 30, 1017-1023.

[7]   Adams, M., Borysiewicz, L., Fiander, A., et al. (2001) Clinical Studies of Human Papillomavirus Vaccines in Pre-Invasive and Invasive Cancer. Vaccine, 19, 2549-2556.
http://dx.doi.org/10.1016/S0264-410X(00)00488-6

[8]   Deacon, J.M., Evans, C.D., Yule, R., et al. (2000) Sexual Behaviour and Smoking as Determinants of Cervical HPV Infection and of CIN 3 among Those Infected: A Case-Control Study Nested within the Manchester Cohort. British Journal of Cancer, 88, 1565-1572.
http://dx.doi.org/10.1054/bjoc.2000.1523

[9]   Ursic-Vrscaj, M., Kovacic, J., Poljak, M. and Marin, J. (1996) Association of Risk Factors for Cervical Cancer and Human Papilloma Viruses in Invasive Cervical Cancer. European Journal of Gynaecological Oncology, 17, 368-371.

[10]   Daling, J.R., Madeleine, M.M., Mc Night, B., et al. (1996) The Relationship of Human Papillomavirus-Related Cervical Tumours to Cigarette Smoking, Oral Contraceptive Use, and Prior Herpes Simplex Virus Type 2 Infection. Cancer Epidemiology, Biomarkers & Prevention, 5, 541-548.

[11]   Cox, J.T. (1995) Epidemiology of Cervical Intraepithelial Neoplasia: The Role of Human Papillomavirus. Clinical Obstetrics and Gynecology, 9, 1-37.

[12]   Lai, H.C., Sytwu, H.K., Sun, C.A., et al. (2003) Single Nucleotide Polymorphism at Fas Promoter Is Associated with Cervical Carcinogenesis. International Journal of Cancer, 103, 221-225.
http://dx.doi.org/10.1002/ijc.10800

[13]   Ueda, M., Terai, Y., Kanda, K., et al. (2006) Fas Gene Promoter-670 Polymorphism in Gynecological Cancer. International Journal of Gynecological Cancer, 16, 179-182.
http://dx.doi.org/10.1111/j.1525-1438.2006.00505.x

[14]   Kordi Tamandani, D.M., Sobti, R.C. and Shekari, M. (2008) Association of Fas-670 Gene Polymorphism with Risk of Cervical Cancer in North Indian Population. Clinical & Experimental Obstetrics & Gynecology, 35, 183-186.

[15]   Zucchi, F., da Silva, I.D., Ribalta, J.C., et al. (2009) Fas/CD95 Promoter Polymorphism Gene and Its Relationship with Cervical Carcinoma. European Journal of Gynaecological Oncology, 30, 142-144.

[16]   Dybikowska, A., Sliwinski, W., Emerich, J. and Podhajska, A.J. (2004) Evaluation of Fas Gene Promoter Polymorphism in Cervical Cancer Patients. International Journal of Molecular Medicine, 14, 475-478.
http://dx.doi.org/10.3892/ijmm.14.3.475

[17]   Engelmark, M.T., Renkema, K.Y. and Gyllesten, U.B. (2004) No Evidence of the Involvement of the Fas-670 Promoter Polymorphism in Cervical Cancer in Situ. International Journal of Cancer, 112, 1084-1085.
http://dx.doi.org/10.1002/ijc.20515

[18]   Zoodsma, M., Nolte, I.M., Schiper, M., et al. (2005) Interleukin-10 and Fas Polymorphism and Susceptibility for (Pre) Neoplastic Cervical Disease. International Journal of Gynecological Cancer, 15, 282-290.
http://dx.doi.org/10.1111/j.1525-1438.2005.00433.x

[19]   Kang, S., Dong, S.M., Seo, S.S., et al. (2008) Fas -1377G/A Polymorlhism and the Risk of Lymph Node Metastasis in Cervical Cancer. Cancer Genetics and Cytogenetics, 180, 1-5.
http://dx.doi.org/10.1016/j.cancergencyto.2007.09.002

[20]   Li, H., Guo, H.Y., Sun, T., et al. (2009) Association between Fas/FasL Genes Promoter Polymorphisms and Pathogenic Risk of Cervical Cancer. Chinese Journal of Oncology, 31, 38-41.

[21]   Schneider, P., Bodmer, J.L., Holler, N., et al. (1997) Characterization of Fas (Apo-1, CD95)—Fas Ligand Interaction. Journal of Biological Chemistry, 272, 18827-18833.
http://dx.doi.org/10.1074/jbc.272.30.18827

[22]   Ashkenazi, A. and Dixit, V.M. (1998) Death Receptors: Signaling and Modulation. Science, 281, 1305-1308.
http://dx.doi.org/10.1126/science.281.5381.1305

[23]   Wajant, H. (2002) The Fas Signaling Pathway: More than a Paradigm. Science, 296, 1635-1636.
http://dx.doi.org/10.1126/science.1071553

[24]   Vaishnaw, A.K., Orlinick, J.R., Chu, J.-L., et al. (1999) The Molecular Basis for Apoptotic Defects in Patients with CD95 (Fas/Apo-1) Mutations. Journal of Clinical Investigation, 103, 355-363.
http://dx.doi.org/10.1172/JCI5121

[25]   Huang, Q.R., Morris, D. and Manopolios, N. (1997) Identification and Characterization of Polymorphisms in the Promoter Region of the Human APO-1/FAS (CD 95) Gene. Molecular Immunology, 34, 577-582.
http://dx.doi.org/10.1016/S0161-5890(97)00081-3

[26]   Huang, Q.R., Danis, V., Lassere, M., et al. (1999) Evaluation of a New Apo-1/Fas Promoter Polymorphism in Rheumatoidd Arthritis and Systemic Lupus Erythematosus Patients. Rheumatology, 38, 645-651.

[27]   Niino, M., Kikuchis, A., Fukazawa, T., et al. (2002) An Examination of the Apo-1/Fas Promoter Mva I Polymorphism in Japanese Patients with Multiple Sclerosis. BMC Neurology, 2, 8-12.
http://dx.doi.org/10.1186/1471-2377-2-8

[28]   Boldrini, L., Faviana, P., Gisfredi, S., et al. (2002) Identification of Fas (Apo-1/CD95) and p53 Gene Mutations in Non-Small Cell Lung Cancer. International Journal of Oncology, 20, 155-159.

[29]   Wang, L.E., Cheng, L., Spitz, M.R. and Wei, Q. (2003) Fas A670G Polymorphism, Apoptotic Capacity in Lymphocyte Cultures, and Risk of Lung Cancer. Lung Cancer, 42, 1-8.
http://dx.doi.org/10.1016/S0169-5002(03)00276-9

[30]   Jrad, B.B.H., Mahfouth, W., Bouaouina, N., et al. (2006) A Polymorphism in Fas Gene Promoter Associated with Increased Risk of Nasopharyngeal Carcinoma and Correlated with Anti-Nuclear Autoantibodies Induction. Cancer Letters, 233, 21-27.
http://dx.doi.org/10.1016/j.canlet.2005.02.037

[31]   Ueda, M., Hung, Y.-C., Terai, Y., et al. (2005) Fas Gene Promoter-670 Polymorphism (A/G) Is Associated with Cervical Carcinogenesis. Gynecologic Oncology, 98, 129-133.
http://dx.doi.org/10.1016/j.ygyno.2005.04.001

[32]   Ferreira, J.A.S. (1999) Perimenopause. In: Fernandes, C.E., Demelo, N.R. and Wehba, S., Eds., Climateric Women: Pathophysiology, Diagnosis and Treatment, Lemos Editorial, Sao Paulo, 13-26.

[33]   FIGO Committee on Gynecologic Oncology, Benedet, J.L., Bender, H., Jones, H., et al. (2000) FIGO Staging Classifications and Clinical Practice Guidelines in the Management of Gynecologic Cancers. International Journal of Gynecology & Obstetrics, 70, 209-262.
http://dx.doi.org/10.1016/S0020-7292(00)90001-8

[34]   Rudert, F., Visser, E., Forbes, L., et al. (1995) Identification of a Silencer, Enhancer, and Basal Promoter Region in the Human CD95 (Fas/Apo-1) Gene. DNA and Cell Biology, 14, 931-937.
http://dx.doi.org/10.1089/dna.1995.14.931

[35]   Adams, M.D., Fieldas, C. and Venter, J.C. (1994) Automated DNA Sequencing and Analysis. Academic Press, San Diego.

[36]   Breslow, N.E. and Day, N.E. (1980) Statistical Methods in Cancer Research—The Analysis of Case-Control Studies. .IARC Sci Publ, 32, 5-338.

[37]   Bosch, F.X. and De Sanjose, S. (2002) Human Papillomavirus in Cervical Cancer. Current Oncology Reports, 4, 175-183.
http://dx.doi.org/10.1007/s11912-002-0079-y

[38]   Lee, S.H., Shin, M.S., Park, W.S., et al. (1999) Alterations of Fas (Apo-1/CD95) Gene in Transitional Cell Carcinomas of Urinary Bladder. Cancer Research, 27, 3068-3072.

[39]   Lee, S.H., Shin, M.S., Park, W.S., et al. (1999) Alterations of Fas (Apo-1/CD95) Gene in Non-Small Cell Lung Cancer. Oncogene, 18, 3754-3760.
http://dx.doi.org/10.1038/sj.onc.1202769

[40]   Nelson, H.H., Kelsey, K.T., Bronson, M.H., et al. (2001) Fas/Apo-1 Promoter Polymorphism Is Not Associated with Non-Melanoma Skin Cancer. Cancer Epidemiology, Biomarkers & Prevention, 10, 809-810.

[41]   Seo, J.C., Han, S.W., Yin, C.S., et al. (2002) Evaluatin of a Apo-1/Fas Promoter Polymorphism in Korean Stroke Patients. Experimental & Molecular Medicine, 34, 294-298.
http://dx.doi.org/10.1038/emm.2002.41

[42]   Lai, H.C., Lin, W.Y., Lin, Y.M., et al. (2005) Genetic Polymorphisms of FAS and FASL (CD95/CD95L) Genes in Cervical Carcinogenesis: An Analysis of Haplotype and Gene-Gene Interaction. Gynecologic Oncology, 99, 113-118.
http://dx.doi.org/10.1016/j.ygyno.2005.05.010

[43]   Park, S.H., Choi, J.E., Kim, E.J., et al. (2006) Polymorphisms in the FAS and FASL Genes and Risk of Lung Cancer in a Korean Population. Lung Cancer, 54, 303-308.
http://dx.doi.org/10.1016/j.lungcan.2006.09.002

[44]   Li-Weber, M. and Krammer, P.H. (2003) Function and Regulation of the CD95 (Apo-1/Fas) Ligand in the Immune System. Seminars in Immunology, 15, 145-157.
http://dx.doi.org/10.1016/S1044-5323(03)00030-7

[45]   Sepiashvili, R.A., Shubich, M.G., Kolesnikova, N.V., et al. (2001) Apoptosis in Immunologic Process. Clinical and Applied Immunology Reviews, 1, 163-172.
http://dx.doi.org/10.1016/S1529-1049(01)00024-1

[46]   Mor, G., Straszewski, S. and Kamsteeg, M. (2002) Role of the Fas/Fas Ligand System in Female Reproductive Organs: Survival and Apoptosis. Biochemical Pharmacology, 64, 1305-1315.
http://dx.doi.org/10.1016/S0006-2952(02)01267-4

[47]   Butler, L.M., Hewett, P.J., Butler, W.J. and Cowled, P.A. (1998) Down-Regulation of Fas Gene Expresson in Colon Cancer Is Not a Result of Allelic Loss or Gene Rearrangement. British Journal of Cancer, 77, 154-159.
http://dx.doi.org/10.1038/bjc.1998.239

[48]   Shimonishi, T., Isse, K., Shibata, F., et al. (2000) Up-Regulation of Fas Ligand at Early Stages and Down-Regulation of Fas at Progressed Stages of Intrahepatic Cholangiocarcinoma Reflect Evasion from Immune Surveillance. Hepatology, 32, 761-769.
http://dx.doi.org/10.1053/jhep.2000.18192

[49]   Lee, Y.H., Kim, Y.R., Ji, J.D., et al. (2001) Fas Promoter-670 Polymorphism Is Associated with Development of Anti-RNP Antibodies in Systemic Lupus Erythematosus. The Journal of Rheumatology, 28, 2008-2011.

[50]   Das, H., Koizumi, T., Sugimoto, T., et al. (2000) Quantitation of Fas and Fas Ligand Gene Expression in Human Ovarian, Cervical and Endometrial Carcinomas Using Real-Time Quantitative RT-PCR. British Journal of Cancer, 82, 1682-1688.

[51]   Sun, T., Zhou, Y., Li, H., et al. (2005) FASL -844C Polymorphism Is Associated with Increased Activation-Induced T Cell Death and Risk of Cervical Cancer. The Journal of Experimental Medicine, 202, 967-974.
http://dx.doi.org/10.1084/jem.20050707

[52]   Schiffman, M.H. and Castle, P.E. (2003) Human Papillomavirus: Epidemiology and Public Health. Archives of Pathology & Laboratory Medicine, 127, 930-934.

[53]   Au, W.W., Sierra-Torres, C.H. and Tyring, S.K. (2003) Acquired and Genetic Susceptibility to Cervical Cancer. Mutation Research, 544, 361-364.
http://dx.doi.org/10.1016/j.mrrev.2003.05.001

[54]   Zhang, X., Miao, X., Sun, T., et al. (2005) Functional Polymorphisms in Cell Death Pathway Genes FAS and FASL Contribute to Risk of Lung Cancer. Journal of Medical Genetics, 42, 479-484.
http://dx.doi.org/10.1136/jmg.2004.030106

[55]   Sun, T., Miao, X., Zhang, X., et al. (2004) Polymorphism of Death Pathway Genes FAS and FASL in Esophageal Squamous Cell Carcinoma. Journal of the National Cancer Institute, 96, 1030-1036.
http://dx.doi.org/10.1093/jnci/djh187

[56]   Suzuki, N., Wakisoka, S., Tokeba, Y., et al. (1999) Effects of Cigarette Smoking on Fas/Fas Ligand Expression of Human Lymphocytes. Cellular Immunology, 25, 48-53.
http://dx.doi.org/10.1006/cimm.1998.1432

[57]   Bijl, M., Horst, G., Limburg, P.C. and Kallemberg, C.G. (2001) Effects of Smoking on Activation Markers, Fas Expression and Apoptosis of Peripheral Blood Lymphocytes. European Journal of Clinical Investigation, 31, 550-553.
http://dx.doi.org/10.1046/j.1365-2362.2001.00842.x

[58]   Winkelstein Jr, W. (1990) Smoking and Cervical Cancer—Currents Status: A Review. American Journal of Epidemiology, 131, 945-957.

[59]   Simons, A.M., Phillips, D.H. and Coleman, D.V. (1993) Damages to DNA in Cervical Epithelium Related to Smoking Tobacco. The BMJ, 306, 1444-1448.
http://dx.doi.org/10.1136/bmj.306.6890.1444

[60]   Schiffman, M., Bauer, H., Hoover, R., et al. (1993) Epidemiologic Evidence Showing That Human Papillomavirus Infection Causes Most Cervical Intraepithelial Neoplasia. Journal of the National Cancer Institute, 85, 958-964.
http://dx.doi.org/10.1093/jnci/85.12.958

[61]   Eluf-Neto, J., Booth, M., Munoz, N., et al. (1994) Human Papillomavirus and Invasive Cervical Cancer in Brazil. British Journal of Cancer, 69, 114-119.
http://dx.doi.org/10.1038/bjc.1994.18

[62]   Moreno, V., Bosch, F.X., Munoz, N., et al. (2002) Effect of Oral Contraceptives on risk of Cervical Cancer in Women with Human Papillomavirus Infection: The IARC Multicentric Case-Control Study. The Lancet, 359, 1085-1092.
http://dx.doi.org/10.1016/S0140-6736(02)08150-3

[63]   Eppel, W., Worda, C., Frigo, P., et al. (2000) Human Papillomavirus in the Cervix and Placenta. Obstetrics & Gynecology, 96, 337-341.
http://dx.doi.org/10.1016/S0029-7844(00)00953-4

[64]   Vaux, D.L. and Flavell, R.A. (2000) Apoptosis Genes and Autoimmunity. Current Opinion in Immunology, 12, 719-724.
http://dx.doi.org/10.1016/S0952-7915(00)00168-0

[65]   Jackson, C.E., Fischer, R.E., Hsu, A.P., et al. (1999) Autoimmune Lymphoproliferative Syndrome with Defective Fas: Genotype Influences Penetrance. The American Journal of Human Genetics, 64, 1002-1014.
http://dx.doi.org/10.1086/302333

[66]   Resqué, R.L., Freitas, N.S.C., Rodrigues, E.M.R., et al. (2010) Estimates of Interethnic Admixture in the Brazilian Population Using a Panel of 24 X-Linked Insertion/Deletion Markers. American Journal of Human Biology, 22, 849-852.
http://dx.doi.org/10.1002/ajhb.21089

 
 
Top